The liver plays a key role in regulating total body energy homeostasis and its ability to do so is greatly affected by the occurrence of pathological conditions such as hepatosteatosis or non-alcoholic fatty liver disease (NAFLD), which contributes to hepatic insulin resistance and potentially end-stage liver disease-related mortality. Triglyceride accumulation in hepatocytes of steatotic livers results from the incorporation of plasma free fatty acids as well as de novo fat synthesis.
Non-alcoholic fatty liver disease (NAFLD) is the term for a wide range of conditions caused by a build-up of fat within the liver cells. It is usually seen in people who are overweight or obese. If the build-up of fat increases, inflammation and scarring of the liver may occur.
People who are obese and have NAFLD are more at risk of suffering from a heart attack or a stroke. Indeed NAFLD is associated with; obesity; type II diabetes; high blood pressure; and high cholesterol.
Treatment of NAFLD involves weight loss and exercise; reducing the levels of triglycerides in the blood and reducing the level of glucose in the blood.
There are currently no specific medicines for NAFLD, but certain medicines used to treat high blood pressure and diabetes also have a beneficial effect on the liver. NAFLD may go on to cause cirrhosis or liver cancer and as such early and effective treatment is essential.
The primary goal for the clinical management of NAFLD is to reduce the risk of cardiovascular disease and type II diabetes. The risks of these diseases are highly diminished by reducing triglyceride levels in the blood including LDL cholesterol, reducing blood pressure, and reducing blood glucose levels.
Triglycerides (TG) are fat molecules which circulate in the blood, and are used to provide energy to the body, but excess TG which are not used are stored. High triglyceride levels are linked to a greater chance of heart disease and other metabolic disorders.
Triglycerides are the end product of digesting and breaking down fats in meals. Some triglycerides are made in the body from other energy sources such as carbohydrates. A healthy diet and exercise plan can lower triglyceride levels, improve cholesterol, and lower the risk of heart disease although this is sometimes difficult to achieve.
High triglyceride levels can also be caused by mediations such as beta blockers; ACE inhibitors; diuretics; hormonal contraceptives; immunosuppressants; HIV treatments; and anti-psychotics.
Lowering TG levels in the blood can help reduce the risk of suffering from heart disease, diabetes and other metabolic disorders.
It has been shown previously that tetrahydrocannabivarin (THCV) is able to decrease triglyceride levels in HHL-5 cells treated with oleic acid. This is an in vitro model for fatty liver disease which showed that THCV was able to reduce triglyceride (TG) levels in a time dependent manner (Wargent et al., 2013).
It has also been suggested that cannabidiol (CBD) may be useful in reducing TG levels in blood (WO 2009/093018).
Yang et al. (2014) describes that CBD may protect the liver from the effects of binge alcohol-induced steatosis.
The Polish patent application PL 388833 describes the use of CBD for reducing body weight gain and reducing excessive fat accumulation.
Surprisingly, it has now been found that a metabolite of CBD, 7-hydroxy-cannabidiol, (7-OH CBD) is able to decrease intracellular TG levels in an in vitro model of fatty liver disease; furthermore it was more potent than its parent compound CBD. Conversely a metabolite of THCV, 11-hydroxy-tetrahydrocannabivarin, (11-OH-THCV) had no effect on the TG levels which infers that not all metabolites are effective in the same way as their parent compounds.